Autofluorescent Flavoprotein Imaging of Intraepidermal Nerve Fibers: a Pilot Study

NCT ID: NCT02537951

Last Updated: 2019-06-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-09-30
• Study Completion Date: 2016-09-30

Brief Summary

Small fiber neuropathy (SFN) is a common disorder, which has a profound negative impact on quality of life because of severe neuropathic pain. To reliably establish a diagnosis of SFN is challenging, since neurological examination and nerve conduction studies are often normal. Autofluorescent flavoprotein imaging (AFI) is an optical method through which neuronal activity in the termination area of small nerve fibers in the spinal cord can be quantified. Since the epidermis also contains a high density of small nerve terminals and since the number of intraepidermal nerve fibers is greatly reduced in patients with SFN, our hypothesis is that AFI intensity is reduced in patients with SFN. To support this hypothesis, a pilot study is required in which the investigators first need to confirm the precision of AFI in the epidermis of the third finger of 10 healthy volunteers. Secondly, lidocaine/prilocaine cream will be used as a negative control. Finally, the AFI signal will be measured after application of a 8% capsaicin patch, through which (temporarily) a selective reduction of small nerve fibers can be induced, mimicking SFN. Using this experimental design, the investigators will be able to test the reliability and validity of AFI for capsaicin-induced small nerve fiber degeneration. This would be a significant step in developing an objective, rapid and non-invasive diagnostic tool to diagnose patients with SFN, which may also be utilized as a biomarker in studies that assess the efficacy of novel treatments for SFN.

Detailed Description

The first aim of the current project is to test the precision of AFI in the epidermis of 10 healthy volunteers. For this purpose, a range of nociceptive electrical stimuli with increasing intensities (5Hz @ 0.5mA-1.0mA) and one innocuous control stimulus (2000Hz @1mA) will be delivered to the third finger of each subject. The outcome measure is AFI-intensity, which is the change in autofluorescence intensity compared to baseline (delta F/F). The standard deviation of AFI intensity will be the measure of precision. Pearson's correlation coefficient will be calculated between electrical stimulus intensities and AFI intensity. A linear correlation needs to be confirmed, since this is a general characteristic of AFI. A paired t-tests will be performed to compare AFI intensities following 5Hz @ 1mA stimulation and 2000Hz @ 1mA stimulation. Lidocaine/prilocaine cream will be applied to the fingertips of the subjects and the electrical stimuli will be repeated, to serve as a negative control experiment. A repeated-measures ANOVA will be performed to compare AFI intensities before and after application of lidocaine/prilocaine cream.

The second aim of our study is to validate AFI in experimentally induced small nerve fiber degeneration of the epidermis, by comparing AFI intensities in subjects before and one week after application of a 8% capsaicin patch to the third fingertip. A repeated-measures ANOVA will be performed to compare AFI intensities before and after capsaicin-induced small nerve fiber degeneration. Assuming that all subjects develop epidermal small fiber degeneration following the 8% capsaicin patch, a statistically significant difference in AFI intensity would serve as a proof-of-principle and would provide validity to autofluorescent flavoprotein imaging of epidermal nociceptor activity as a diagnostic test for SFN. Comparing the distributions of before and after capsaicin-induced small nerve fiber degeneration will lead to a probability estimation of having SFN based on the outcome measure, i.e. AFI intensity. In future research, false-positive and false-negative consequences will be evaluated, leading to cut-off values in patients suspected for SFN.

Conditions

Small Fiber Neuropathy

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

AFI intensity in healthy volunteers

10 healthy volunteers, on whose 3rd fingertips AFI intensity is measured through an AFI microscope

Group Type: EXPERIMENTAL

AFI microscope

Intervention Type: DEVICE

measurement of AFI intensities following increasing nociceptive stimulus intensities

negative control 1: lidocaine/prilocaine

10 healthy volunteers, on whose 3rd fingertips AFI intensity is measured through an AFI microscope, 1hour after application of lidocaine/prilocaine creme (negative control 1)

Group Type: ACTIVE_COMPARATOR

negative control 1: lidocaine/prilocaine

Intervention Type: DEVICE

measurement of AFI intensities following lidocaine/prilocaine cream

negative control 2: 8% capsaicin

-10 healthy volunteers, on whose 3rd fingertips AFI intensity is measured through an AFI microscope, 1week after application of an 8% capsaicin patch (negative control 2)

Group Type: ACTIVE_COMPARATOR

negative control 2: 8% capsaicin

Intervention Type: DEVICE

measurement of AFI intensities following 8% capsaicin patch

Interventions

AFI microscope

measurement of AFI intensities following increasing nociceptive stimulus intensities

Intervention Type: DEVICE

negative control 1: lidocaine/prilocaine

measurement of AFI intensities following lidocaine/prilocaine cream

Intervention Type: DEVICE

negative control 2: 8% capsaicin

measurement of AFI intensities following 8% capsaicin patch

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• healthy volunteers

Exclusion Criteria

• younger than 18 years
• pre-existing neuropathy
• previous allergic reaction to local anaesthetics

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Erasmus Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Joost LM Jongen

Dr. J.L.M. Jongen, neurologist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Joost LM Jongen, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Erasmus Medical Center

Locations

Dept. Neurology, Erasmus MC

Rotterdam, , Netherlands

Countries

Netherlands

Provided Documents

Document Type: Study Protocol

View Document

Other Identifiers

NL49568.078.14

Identifier Type: -

Identifier Source: org_study_id